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Clinical Orthopaedics and Related... Jul 2014Tumors of the appendicular skeleton commonly affect the proximal humerus, but there is no consensus regarding the best reconstructive technique after proximal humerus... (Review)
Review
BACKGROUND
Tumors of the appendicular skeleton commonly affect the proximal humerus, but there is no consensus regarding the best reconstructive technique after proximal humerus resection for tumors of the shoulder.
QUESTIONS/PURPOSES
We wished to perform a systematic review to determine which surgical reconstruction offers the (1) best functional outcome as measured by the Musculoskeletal Tumor Society (MSTS) score, (2) longest construct survival, and (3) lowest complication rate after proximal humerus resection for malignant or aggressive benign tumors of the shoulder.
METHODS
We searched the literature up to June 1, 2013, from MEDLINE, EMBASE, and the Cochrane Library. Only studies reporting results in English, Dutch, or German and with followups of 80% or more of the patients at a minimum of 2 years were included. Twenty-nine studies with 693 patients met our criteria, seven studies (24%) were level of evidence III and the remainder were level IV. Studies reported on reconstruction with prostheses (n = 17), osteoarticular allografts (n = 10), and allograft-prosthesis composites (n = 11). Owing to substantial heterogeneity and bias, we narratively report our results.
RESULTS
Functional scores in prosthesis studies ranged from 61% to 77% (10 studies, 141 patients), from 50% to 78% (eight studies, 84 patients) in osteoarticular graft studies, and from 57% to 91% (10 studies, 141 patients) in allograft-prosthesis composite studies. Implant survival ranged from 0.38 to 1.0 in the prosthesis group (341 patients), 0.33 to 1.0 in the osteoarticular allograft group (143 patients), and 0.33 to 1.0 in allograft-prosthesis group (132 patients). Overall complications per patient varied between 0.045 and 0.85 in the prosthesis group, 0 and 1.5 in the osteoarticular graft group, and 0.19 and 0.79 in the prosthesis-composite graft group. We observed a higher fracture rate for osteoarticular allografts, but other specific complication rates were similar.
CONCLUSIONS
Owing to the limitations of our systematic review, we found that allograft-prosthesis composites and prostheses seem to have similar functional outcome and survival rates, and both seem to avoid fractures that are observed with osteoarticular allografts. Further collaboration in the field of surgical oncology, using randomized controlled trials, is required to establish the superiority of any particular treatment.
Topics: Biomechanical Phenomena; Bone Neoplasms; Bone Transplantation; Graft Survival; Humans; Humerus; Osseointegration; Osteotomy; Periprosthetic Fractures; Prosthesis Design; Prosthesis Failure; Prosthesis Implantation; Plastic Surgery Procedures; Recovery of Function; Risk Factors; Time Factors; Transplantation, Homologous; Treatment Outcome
PubMed: 24469551
DOI: 10.1007/s11999-014-3474-4 -
Acta Clinica Croatica Mar 2022The objective of this study was to explore the possible differences in bone mass density (BMD) and markers of bone metabolism between patients with psoriasis with...
The objective of this study was to explore the possible differences in bone mass density (BMD) and markers of bone metabolism between patients with psoriasis with concomitant psoriatic arthritis (PsA) and patients with psoriasis only (PV). A comparable sample of both types of patients were included in analysis. In all patients, vitamin D serum levels along with inflammatory markers and parathyroid hormone (PTH) were measured. BMD was assessed with dual-energy x-ray absorptiometry scan in axial and appendicular skeleton. Patients with PsA tended to have decreased BMD in axial skeleton, while BMD in appendicular skeleton was comparable between the groups. No statistically significant correlation was found of inflammatory markers, vitamin D and PTH levels with BMD in either patient group. A negative correlation was recorded between vitamin D serum concentration and PTH levels.
Topics: Humans; Vitamin D; Bone Density; Arthritis, Psoriatic; Vitamins; Parathyroid Hormone; Minerals; Psoriasis
PubMed: 36398080
DOI: 10.20471/acc.2022.61.01.09 -
Frontiers in Endocrinology 2022Bone marrow adipose tissue (BMAT) is a dynamic tissue which is associated with osteoporosis, bone metastasis, and primary bone tumors. The aim of this study is to...
Gender- and Age-Associated Differences in Bone Marrow Adipose Tissue and Bone Marrow Fat Unsaturation Throughout the Skeleton, Quantified Using Chemical Shift Encoding-Based Water-Fat MRI.
Bone marrow adipose tissue (BMAT) is a dynamic tissue which is associated with osteoporosis, bone metastasis, and primary bone tumors. The aim of this study is to determine region-specific variations and age- and gender-specific differences in BMAT and BMAT composition in healthy subjects. In this cross-sectional study, we included 40 healthy subjects (26 male: mean age 49 years, range 22-75 years; 14 female: mean age 50 years, range 29-71) and determined the bone marrow signal fat fraction and bone marrow unsaturation in the spine (C3-L5), pelvis, femora, and tibiae using chemical shift encoding-based water-fat imaging (WFI) with multiple gradient echoes (mGRE). Regions of interest covered the individual vertebral bodies, pelvis and proximal epimetaphysis, diaphysis, and distal epimetaphysis of the femur and tibia. The spinal fat fraction increased from cervical to lumbar vertebral bodies (mean fat fraction ( ± SD or (IQR): cervical spine 0.37 ± 0.1; thoracic spine 0.41 ± 0.08. lumbar spine 0.46 ± 0.01; p < 0.001). The femoral fat fraction increased from proximal to distal (proximal 0.78 ± 0.09; diaphysis 0.86 (0.15); distal 0.93 ± 0.02; p < 0.001), while within the tibia the fat fraction decreased from proximal to distal (proximal 0.92 ± 0.01; diaphysis 0.91 (0.02); distal 0.90 ± 0.01; p < 0.001). In female subjects, age was associated with fat fraction in the spine, pelvis, and proximal femur (ρ = 0.88 p < 0.001; ρ = 0.87 p < 0.001; ρ = 0.63 p = 0.02; ρ = 0.74 p = 0.002, respectively), while in male subjects age was only associated with spinal fat fraction (ρ = 0.40 p = 0.04). Fat fraction and unsaturation were negatively associated within the spine (r = -0.40 p = 0.01), while in the extremities fat fraction and unsaturation were positively associated (distal femur: r = 0.42 p = 0.01; proximal tibia: r = 0.47, p = 0.002; distal tibia: r = 0.35 p = 0.03), both independent of age and gender. In conclusion, we confirm the distinct, age- and gender-dependent, distribution of BMAT throughout the human skeleton and we show that, contradicting previous animal studies, bone marrow unsaturation in human subjects is highest within the axial skeleton compared to the appendicular skeleton. Furthermore, we show that BMAT unsaturation was negatively correlated with BMAT within the spine, while in the appendicular skeleton, BMAT and BMAT unsaturation were positively associated.
Topics: Adipose Tissue; Animals; Bone Marrow; Bone and Bones; Cross-Sectional Studies; Female; Humans; Lumbar Vertebrae; Magnetic Resonance Imaging; Male; Water
PubMed: 35574007
DOI: 10.3389/fendo.2022.815835 -
Hellenic Journal of Nuclear Medicine 2019Fluorine-18 fluorodeoxyglucose positron emission tomography (F-FDG PET) imaging was conceived in the early 1970 by investigators at the University of Pennsylvania as a...
Fluorine-18 fluorodeoxyglucose positron emission tomography (F-FDG PET) imaging was conceived in the early 1970 by investigators at the University of Pennsylvania as a research technique to measure brain metabolism and function by employing a non-invasive imaging approach. Soon after the introduction of whole-body PET instruments, F-FDG was utilized in the assessment of a variety of solid tumors and certain hematological malignancies. Yet, the role of F-FDG in assessing benign and uncommon malignant disorders of the bone marrow has not been investigated to a great extent. Fluorine-18-FDG as a molecular probe has the proven capacity to reflect the abnormal glycolytic activities inherent to a variety of disorders, where such information may serve as a guide to the clinical course of the respective disease. Recent efforts have studied bone marrow and extra-medullary disease activity in certain malignancies like chronic lymphocytic leukemia. Nonetheless, few studies have explored the role of F-FDG in assessing the metabolic basis of benign disorders of red marrow. Moreover, the introduction of novel imaging analysis schemes in recent years has allowed for the global assessment of red marrow disease, which can provide a superior means for characterizing the systemic nature and burden of these disorders. Accordingly, semi-quantitative global analysis techniques as applied to the skeletal structures in F-FDG PET may provide a tool to better understand these complex marrow abnormalities. Functional imaging of red bone marrow may also reveal critical information specifically regarding the extra-medullary extension of such hematological disorders that cannot be assessed by other diagnostic or imaging techniques. Myleoproliferative neoplasms (MPN) are an apt category of hematological disease that confer significantly altered systemic metabolic rates of hematopoietic stem cells (HSC) in the marrow, as such they are primed for exploration with F-FDG PET. The hallmark of such disorders involves the excess production of particular cellular components in blood. After a period of excess production, scar tissue may develop in place of the HSC leading to myleofibrosis and decreased hematopoietic activity. One of the least studied disorders within the larger category of MPN with respect to the nuclear medicine is polycythemia. Polycythemia may be either primary, polycythemia vera (PV), or secondary. PV involves a JAK2+ in HSC which allows for the excessive proliferation of immature erythrocytes and depressed erythropoietin levels as a result. Secondary polycythemia occurs in response to decreased oxygen intake, often as a result of smoking, which results in increased erythropoietin and hematocrit levels. Primary and secondary polycythemia lead to an increase in overall red marrow activity and a diffusion of active red marrow into the appendicular skeleton. Clinical presentation often includes redness or irritation of the skin along with headache, fatigue and excessive bleeding. Based upon the mentioned precedent, it is evident that PET imaging with F-FDG and other tracers will play a meaningful role in assessing diffuse bone marrow disorders such as hematological malignancies and myeloproliferative abnormalities. Semi-quantification studies of global bone marrow activity in such an application will be a vital means in accurately assessing the systematic nature and global burden of such benign hematological disorders such a polycythemia. Accordingly, the derived metabolic data projects to be a useful tool in the prospective clinical and scientific aspects of the diagnosis of these benign hematological disorders and the assessment of disease progression in light of relevant biological treatments. Given the nature of the disease and the enumerated capabilities of F-FDG PET it is expected that one would be able to capture the systematic abnormalities inherent to the disease. Moreover, the handful of case studies supports this possibility. Three case studies have all illustrated diffuse elevated F-FDG uptake throughout the axial and appendicular skeleton that reflects the hyper-metabolic red bone marrow as related to polycythemia. Moreover, the use of various functional imaging tracers, in addition to F-FDG, may indirectly reflect hypermetabolism in red bone marrow through abnormal tracer accumulation in the skeletons of patients. The whole body F-FDG scan of a JAK2+ PV patient before treatment (a) as compared to a matched subject (b) is found below; of note is the PV patient's elevated uptake in the pelvis, femur and spine.
Topics: Fluorodeoxyglucose F18; Humans; Polycythemia; Positron-Emission Tomography; Radiopharmaceuticals
PubMed: 30843002
DOI: 10.1967/s002449910951 -
Disease Models & Mechanisms Apr 2021Achondroplasia (ACH), the most common form of dwarfism, is caused by a missense mutation in the gene coding for fibroblast growth factor receptor 3 (FGFR3). The...
Achondroplasia (ACH), the most common form of dwarfism, is caused by a missense mutation in the gene coding for fibroblast growth factor receptor 3 (FGFR3). The resulting increase in FGFR3 signaling perturbs the proliferation and differentiation of chondrocytes (CCs), alters the process of endochondral ossification and thus reduces bone elongation. Increased FGFR3 signaling in osteoblasts (OBs) might also contribute to bone anomalies in ACH. In the present study of a mouse model of ACH, we sought to determine whether FGFR3 overactivation in OBs leads to bone modifications. The model carries an Fgfr3-activating mutation (Fgfr3Y367C/+) that accurately mimics ACH; we targeted the mutation to either immature OBs and hypertrophic CCs or to mature OBs by using the Osx-cre and collagen 1α1 (2.3 kb Col1a1)-cre mouse strains, respectively. We observed that Fgfr3 activation in immature OBs and hypertrophic CCs (Osx-Fgfr3) not only perturbed the hypertrophic cells of the growth plate (thus affecting long bone growth) but also led to osteopenia and low cortical thickness in long bones in adult (3-month-old) mice but not growing (3-week-old) mice. Importantly, craniofacial membranous bone defects were present in the adult mice. In contrast, activation of Fgfr3 in mature OBs (Col1-Fgfr3) had very limited effects on skeletal shape, size and micro-architecture. In vitro, we observed that Fgfr3 activation in immature OBs was associated with low mineralization activity. In conclusion, immature OBs appear to be affected by Fgfr3 overactivation, which might contribute to the bone modifications observed in ACH independently of CCs.
Topics: Animals; Bone Diseases, Metabolic; Cell Differentiation; Chondrocytes; Disease Models, Animal; Dwarfism; Face; Growth Plate; Hypertrophy; Mice, Transgenic; Mutation; Osteoblasts; Osteogenesis; Receptor, Fibroblast Growth Factor, Type 3; Skull
PubMed: 33737326
DOI: 10.1242/dmm.048272 -
Clinical Orthopaedics and Related... Sep 2017
Review
Topics: Bone Neoplasms; Bone and Bones; Cartilage; Humans; Oncologists; Orthopedics
PubMed: 28589333
DOI: 10.1007/s11999-017-5399-1 -
Clinical Interventions in Aging 2021The aim of this research was to assess the correlations between the impedance components and the appendicular skeletal muscle strength and functional quality indices in...
PURPOSE
The aim of this research was to assess the correlations between the impedance components and the appendicular skeletal muscle strength and functional quality indices in older adults. The use of the impedance parameters as potential identifiers characterizing the functional state of muscles could improve methods of monitoring "healthy ageing".
PATIENTS AND METHODS
A total of 346 subjectively healthy adults aged 50-83 years were subjected to tests. Body mass and height, hand grip strength and knee extensor strength were measured. Resistance, reactance and phase angle were measured using the bioelectrical impedance method. The relationship between the impedance parameters and the appendicular skeletal muscle strength and quality indices was evaluated using stepwise multiple regression.
RESULTS
Participants aged ≥65 years were found to be characterized by lower values of the impedance parameters and the appendicular skeletal muscle strength and functional quality indices than participants 10 years younger. In both groups of sexes, the relative percentage differences in limb strength between the age groups were 3-6 times greater than the differences in appendicular skeletal muscle mass. Significant regression models for muscle strength and quality, with strong age, sex and reactance prediction and a weaker phase angle effect, were obtained.
CONCLUSION
The impedance components explain the part of changes in muscle strength which is independent of the decline in skeletal muscle mass. Phase angle and reactance can be suitable for diagnosing and preventing dangers connected with the decline in muscle quality, but it is necessary to establish their normalized reference values for older adults.
Topics: Age Factors; Aged; Aged, 80 and over; Body Composition; Body Height; Body Mass Index; Electric Impedance; Female; Hand Strength; Humans; Knee Joint; Male; Middle Aged; Muscle Strength; Muscle, Skeletal; Physical Functional Performance; Poland; Sex Factors
PubMed: 33574661
DOI: 10.2147/CIA.S287373 -
ELife Nov 2022Activation of Wnt signaling leads to high bone density. The R-spondin family of four secreted glycoproteins (Rspo1-4) amplifies Wnt signaling. In humans, RSPO3 variants...
Activation of Wnt signaling leads to high bone density. The R-spondin family of four secreted glycoproteins (Rspo1-4) amplifies Wnt signaling. In humans, RSPO3 variants are strongly associated with bone density. Here, we investigated the role of Rspo3 in skeletal homeostasis in mice. Using a comprehensive set of mouse genetic and mechanistic studies, we show that in the appendicular skeleton, haplo-insufficiency and targeted deletion in osteoprogenitors lead to an increase in trabecular bone mass, with increased number of osteoblasts and bone formation. In contrast and highlighting the complexity of Wnt signaling in the regulation of skeletal homeostasis, we show that deletion in osteoprogenitors results in the opposite phenotype in the axial skeleton, i.e., low vertebral trabecular bone mass. Mechanistically, deficiency impairs the inhibitory effect of Dkk1 on Wnt signaling activation and bone mass. We demonstrate that deficiency leads to activation of Erk signaling which in turn, stabilizes β-catenin and Wnt signaling activation. Our data demonstrate that haplo-insufficiency/deficiency boosts canonical Wnt signaling by activating Erk signaling, to favor osteoblastogenesis, bone formation, and bone mass.
Topics: Humans; Mice; Animals; Wnt Signaling Pathway; Osteogenesis; Phosphorylation; Bone and Bones; Glycoproteins
PubMed: 36321691
DOI: 10.7554/eLife.84171 -
Journal of Orthopaedic Surgery and... Jun 2023It is known that muscle strength and muscle mass play a crucial role in maintaining bone mineral density (BMD). Despite this, there are uncertainties about how muscle...
PURPOSE
It is known that muscle strength and muscle mass play a crucial role in maintaining bone mineral density (BMD). Despite this, there are uncertainties about how muscle mass, lower extremity muscular strength, and BMD are related. We examined the impact of lower extremity muscle strength and mass on BMD in the general American population using cross-sectional analysis.
METHODS
In the study, we extracted 2165 individuals from the National Health and Nutrition Examination Survey 1999-2002. Multivariate logistic regression models were used to examine the association between muscle strength, muscle mass, and BMD. Fitted smoothing curves and generalized additive models were also performed. To ensure data stability and avoid confounding factors, subgroup analysis was also conducted on gender and race/ethnicity.
RESULTS
After full adjustment for potential confounders, significant positive associations were detected between peak force (PF) [0.167 (0.084, 0.249) P < 0.001], appendicular skeletal muscle index (ASMI) [0.029 (0.022, 0.036) P < 0.001], and lumbar spine BMD. A positive correlation was also found between PF, ASMI, and pelvis and total BMD. Following stratification by gender and race/ethnicity, our analyses illustrated a significant correlation between PF and lumbar spine BMD in both men [0.232 (0.130, 0.333) P < 0.001] and women [0.281 (0.142, 0.420) P < 0.001]. This was also seen in non-Hispanic white [0.178 (0.068, 0.288) P = 0.002], but not in non-Hispanic black, Mexican American and other race-ethnicity. Additionally, there was a positive link between ASMI and BMD in both genders in non-Hispanic whites, and non-Hispanic blacks, but not in any other racial group.
CONCLUSION
PF and ASMI were positively associated with BMD in American adults. In the future, the findings reported here may have profound implications for public health in terms of osteopenia and osteoporosis prevention, early diagnosis, and treatment.
Topics: Adult; Humans; Female; Male; Bone Density; Nutrition Surveys; Cross-Sectional Studies; Muscle Strength; Lumbar Vertebrae; Absorptiometry, Photon; White
PubMed: 37264353
DOI: 10.1186/s13018-023-03877-4 -
PloS One Apr 2011During limb development, chondrocytes and osteoblasts emerge from condensations of limb bud mesenchyme. These cells then proliferate and differentiate in separate but...
BACKGROUND
During limb development, chondrocytes and osteoblasts emerge from condensations of limb bud mesenchyme. These cells then proliferate and differentiate in separate but adjacent compartments and function cooperatively to promote bone growth through the process of endochondral ossification. While many aspects of limb skeletal formation are understood, little is known about the mechanisms that link the development of undifferentiated limb bud mesenchyme with formation of the precartilaginous condensation and subsequent proliferative expansion of chondrocyte and osteoblast lineages. The aim of this study was to gain insight into these processes by examining the roles of c-Myc and N-Myc in morphogenesis of the limb skeleton.
METHODOLOGY/PRINCIPAL FINDINGS
To investigate c-Myc function in skeletal development, we characterized mice in which floxed c-Myc alleles were deleted in undifferentiated limb bud mesenchyme with Prx1-Cre, in chondro-osteoprogenitors with Sox9-Cre and in osteoblasts with Osx1-Cre. We show that c-Myc promotes the proliferative expansion of both chondrocytes and osteoblasts and as a consequence controls the process of endochondral growth and ossification and determines bone size. The control of proliferation by c-Myc was related to its effects on global gene transcription, as phosphorylation of the C-Terminal Domain (pCTD) of RNA Polymerase II, a marker of general transcription initiation, was tightly coupled to cell proliferation of growth plate chondrocytes where c-Myc is expressed and severely downregulated in the absence of c-Myc. Finally, we show that combined deletion of N-Myc and c-Myc in early limb bud mesenchyme gives rise to a severely hypoplastic limb skeleton that exhibits features characteristic of individual c-Myc and N-Myc mutants.
CONCLUSIONS/SIGNIFICANCE
Our results show that N-Myc and c-Myc act sequentially during limb development to coordinate the expansion of key progenitor populations responsible for forming the limb skeleton.
Topics: Animals; Bone Development; Bone and Bones; Cell Count; Cell Differentiation; Cell Proliferation; Chondrocytes; Core Binding Factor Alpha 1 Subunit; Gene Deletion; Growth Plate; Limb Buds; Mesoderm; Mice; Mice, Inbred C57BL; Models, Biological; Neovascularization, Physiologic; Nuclear Proteins; Osteogenesis; Proto-Oncogene Proteins c-myc; SOX9 Transcription Factor; Stem Cells; Vascular Endothelial Growth Factor A
PubMed: 21494559
DOI: 10.1371/journal.pone.0018795